OBJECTIVE Shared decision-making supported by patient decisions aids may improve care and reduce healthcare costs for persons considering total joint replacement. Observational study and randomized controlled trials (RCTs) have evaluated the short-term impact of decision aids on uptake of surgery and costs, however the long-term effects are unclear. This analysis aimed to evaluate the effect of patient decision aids on 1) use of joint replacement up to 7-years of follow-up, and 2) osteoarthritis-related health system costs. METHODS 324 participants in a Canadian RCT with 2-years follow-up who were randomized to either a decision aid (n&nbsp;=&nbsp;161) or usual care (n&nbsp;=&nbsp;163) had their trial and health administrative data linked. The proportion undergoing surgery up to 7-years were compared using cumulative incidence plots and competing risk regression. Mean per-patient costs were compared using two sample t-tests. RESULTS At 2-years, 119 of 161 (73.9%) patients in the decision aid arm and 129 of 163 (79.1%) patients in the usual care arm had surgery. Between two and 7-years, 17 additional patients in both the decision aid (of 42, 40.4%) and usual care (of 34, 50.0%) arms underwent surgery. At 7-years, patients exposed to decision aids had a similar likelihood of undergoing surgery (HR&nbsp;=&nbsp;0.92, 95% CI0.73 to 1.17, p&nbsp;=&nbsp;0.49) and mean per-patient costs ($21,965 vs $23,681, incremental cost -$1,717, 95% CI-$5,631 to $2,198) compared to those in usual care. CONCLUSIONS This is the first study to assess the long-term impact of decision aids on use of joint replacement and healthcare costs. These results are not conclusive but can inform future trial design. CLINICAL TRIAL REGISTRATION The full trial protocol is available at ClinicalTrials.Gov (NCT00911638). OBJECTIVE The innate immune system plays a central role in osteoarthritis (OA). We identified 14-3-3ε as a novel mediator that guides chondrocytes toward an inflammatory phenotype. 14-3-3ε shares common characteristics with alarmins. These endogenous molecules, released into extracellular media, are increasingly incriminated in sustaining OA inflammation. Alarmins bind mainly to TLR2 and TLR4 receptors and polarize macrophages in the synovium. We investigated the effects of 14-3-3ε in joint cells and tissues and its interactions with TLRs to define it as a new alarmin involved in OA. DESIGN Chondrocyte, synoviocyte and macrophage cultures from murine or OA human samples were treated with 14-3-3ε. To inhibit TLR2/4 in chondrocytes, blocking antibodies were used. Moreover, chondrocytes and bone marrow macrophage (BMM) cultures from KO TLRs mice were stimulated with 14-3-3ε. Gene expression and release of inflammatory mediators (IL-6, MCP-1, TNFα) were evaluated via RT-qPCR and ELISA. RESULTS In vitro, 14-3-3ε induced gene expression and release of IL6 and MCP1 in the treated cells. The inflammatory effects of 14-3-3ε were significantly reduced following TLRs inhibition or in TLRs KO chondrocytes and BMM. CONCLUSIONS 14-3-3ε is able to induce an inflammatory phenotype in synoviocytes, macrophages and chondrocytes in addition to polarizing macrophages. These effects seem to involve TLR2 or TLR4 to trigger innate immunity. https://www.selleckchem.com/products/AV-951.html Our results designate 14-3-3ε as a novel alarmin in OA and as a new target either for therapeutic and/or prognostic purposes. BACKGROUND The role of intra-articular mineralization in osteoarthritis (OA) is unclear. Its understanding may potentially advance our knowledge of knee OA pathogenesis. We describe and assess the reliability of a novel computed tomography (CT) scoring system, the Boston University Calcium Knee Score (BUCKS) for evaluating intra-articular mineralization. METHODS We included subjects from the most recent study visit of the Multicenter Osteoarthritis Study (MOST) Study, a NIH-funded longitudinal cohort of community-dwelling older adults with or at risk of knee OA. All subjects underwent CT of bilateral knees. Each knee was scored at 28 scored locations (14 for cartilage, 6 for menisci, 6 for ligaments, 1 for joint capsule, and 1 popliteal-tibial vessels). A single musculoskeletal radiologist scored cartilage and meniscus subregions, as well as vascular calcifications assigning to each a score ranging from 0-3. The joint capsule, medial and lateral posterior meniscal roots, ACL/PCL and 2 collateral ligaments (MCL/LCL) were each scored 0 or 1 for absence or presence of mineralization. To assess reliability, 31 subject CTs were reread 12 weeks later by the same reader and by a second reader and agreement was evaluated using a weighted kappa. RESULTS The intra-reader reliability ranged from 0.92 for ligaments to 1.0 for joint capsule. The inter-reader reliability ranged from 0.94 for cartilage and ligaments, to 1.0 for joint capsule. CONCLUSION BUCKS demonstrated excellent reliability and is a potentially useful CT-based tool for studying the role of calcium crystals in knee OA. An alteration of oxytocin signaling during postnatal maturation of the brain could be associated with etiology of neurodevelopmental disorders among them autism. The aim of the present study was to examine the role of oxytocin in the regulation of expression of selected cell-adhesion molecules and scaffolding proteins in the hippocampus in early rat development. Oxytocin treatment (1?mg/ml, i.p., 50?μl/pup) at postnatal days P2-P3 resulted in the reduction of Neuroligin 3 gene expression, and was accompanied by lower SHANK1 and SHANK3 mRNA levels in the hippocampus at P5 day. Immunostaining revealed a clear trend for the lower density of Neuroligin 3 positive cells in the hippocampus and this trend has been significant in the CA3 hippocampal area. The significantly lower Neurexin 2β mRNA levels were observed in response to oxytocin treatment, with no effect seen in the Neurexin 2α gene expression. No change has been observed in the gene expression of Neuroligin 1 and Neuroligin 2. Oxytocin induced an increase in the mRNA levels of Neuron-Specific Enolase (NSE) and a decrease in the mRNA levels of glial fibrillary acid protein (GFAP) - marker of astrocytes. Incubation of primary neuronal cells with oxytocin (1 μM, 48?h) stimulated a proliferation of NSE-positive cells. These results suggest that synaptic proteins could be under control of oxytocin in early stages of brain development. The changes of cell-adhesion molecule and scaffolding protein levels might be linked to the modulation of number of neuronal cells.